Abstract

Because attempts to scale up the published synthetic preparation of p-aminophenethylspiperone (NAPS) by N-alkylation of spiperone with 4-nitrophenethyl bromide followed by reduction gave poor yields and difficulties during purification, an alternative synthetic approach has been developed. Use of 4-(N-tert-butyloxycarbonyl) aminophenethyl bromide to alkylate spiperone followed by the Boc group deprotection gave NAPS in 56% yield. This procedure provides an improved and efficient synthesis of the important high-affinity, selective D2-dopamine receptor antagonist NAPS.